Publication highlights

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Explore a selection of research case studies from the past five years.

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Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

Green, magenta and blue fluorescent image showing the villi in the mouse intestine

Key gene identified for regeneration and repair of mouse intestine

Wear-and-tear means the lining of the gut is continually refurbished. Gut stem cells self-renew or differentiate (change state) into transit amplifying (TA) cells, which in turn either cycle or differentiate into mature gut epithelial cells. TA cells have an additional superpower: they can de-differentiate to replenish the stem cell pool after damage. Vivian Li's lab have found that when ARID3A is knocked out in mice, there are more mature cells and fewer TA cells, as the balance between the two states is disturbed. Further, the ability to repair irradiation-induced damage to the stem cell pool is hampered as damaged stem cells cannot be replaced efficiently from the depleted TA cell pool. These findings reveal the hitherto unrecognised role of ARID3A in coordinating the gut proliferation–differentiation ratio important for both steady-state and injury-induced gut regeneration.

Loss of ARID3A perturbs intestinal epithelial proliferation-differentiation ratio and regeneration

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Published in Journal of Experimental Medicine

Published

Organoids

Stem cells collected in late pregnancy herald advances in prenatal medicine

Researchers from the Li lab worked with scientists at UCL and Great Ormond Street Hospital to develop organoids grown from human stem cells during an active pregnancy, raising the possibility of monitoring and treating congenital conditions before birth. The researchers extracted and characterised live cells from amniotic fluid samples taken from 12 pregnancies as part of routine diagnostic testing. They then used single-cell RNA sequencing to identify which tissues these stem cells came from. Stem cells from the lungs, kidneys and intestine were successfully extracted, which were used to grow organoids that had functional features of these tissue types. These organoids could be used to better study what happens in development both in health and disease.

Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids

Published in Nature Medicine

Published

Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure

Children with intestinal failure cannot absorb the nutrients that are essential to be healthy. In the most severe cases, patients may require transplantation. However, there is a shortage of donor organs and complications can arise after surgery. We have shown how intestinal stem cells and intestinal tissues taken from patients can be used to grow functioning intestinal grafts in the laboratory, which could offer a safe and longer-lasting alternative to traditional donor transplants.

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Published in Nature Medicine

Published

Metabolic precision labeling enables selective probing of O-linked N-acetylgalactosamine glycosylation

The first publication from our group at the Crick comprises the development of a precision tool to understand O-GalNAc glycosylation, one of the most abundant and disease-relevant types of glycans. We apply the technique to run state-of-the-art methods of biology, including chemical glycoproteomics with the Proteomics STP and a genome-wise CRISPR screen with collaborators from Stanford. We also collaborate in-house with Vivian Li to apply the probe to imaging intestinal organoids.

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Published in Proceedings of the National Academy of Sciences of the United States of America

Published

Microscopic image of a mouse colon.

The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity

This paper demonstrates a cell intrinsic role for AHR in intestinal stem cells. AHR deficiency in intestinal epithelium causes dysregulation of the Wnt pathway, overproliferation of crypt stem cells and impaired epithelial differentiation following injury, culminating in tumorigenesis.

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Published in Immunity

Published

Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy

Targeting the nutritional requirements of cancers through selective dietary intervention is an emerging therapeutic approach. Dietary limitation of the non-essential amino acids serine and glycine can limit the growth of some, but not all, cancers. This study extends this approach by showing combined treatment with an inhibitor of the intrinsic serine synthesis pathway with a serine/glycine free diet improves the therapeutic response and inhibits the growth of cancers that are not responsive to the diet alone. Extension of this work to human studies may offer an important new avenue for the treatment of a broad range of cancers.

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Published in Nature Communications

Published

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Research case studies 

Explore a selection of recent case studies that spotlight particular areas of research at the Crick.